ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.5219G>A (p.Trp1740Ter)

dbSNP: rs137854219
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000388680 SCV000330441 pathogenic not provided 2016-04-19 criteria provided, single submitter clinical testing The W1740X nonsense variant in the TSC2 gene has been reported previously in association with tuberous sclerosis complex (TSC) (TSC2 LOVD). Additionally, a different nucleotide substitution, c.5220 G>A, resulting in the same nonsense variant has also been reported in association with TSC (Roberts et al., 2002). The W1740X variant is predicted to cause loss of normal protein function through protein truncation as the last 68 amino acids of the tuberin protein are lost. Therefore, the presence of W1740X is consistent with a diagnosis of TSC
Labcorp Genetics (formerly Invitae), Labcorp RCV001852882 SCV002236315 pathogenic Tuberous sclerosis 2 2024-10-30 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp1740*) in the TSC2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 68 amino acid(s) of the TSC2 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of tuberous sclerosis complex (PMID: 12136241, 31856217). ClinVar contains an entry for this variant (Variation ID: 49362). This variant disrupts a region of the TSC2 protein in which other variant(s) (p.Arg1745Glnfs*27) have been determined to be pathogenic (internal data). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Tuberous sclerosis database (TSC2) RCV000042622 SCV000066416 not provided Tuberous sclerosis syndrome no assertion provided curation

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.